|Phase II||Treatment||Closed||15 to 59||NCI||NCI-2009-00436|
CALGB 10001/SWOG C10001, U10CA031946, CALGB-C10001, CALGB-10001, NCT00039377
This phase II trial is studying how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Combining imatinib mesylate with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia (ALL)
Further Study Information
I. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in ALL patients with t(9;22).
II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by RT-PCR following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.
IV. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).
V. Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).
VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.
OUTLINE: This is a multicenter study.
COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a CALGB/SWOG protocol prior to enrollment.
COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.
COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.
COURSE IV (imatinib mesylate): After blood counts recover after completion of course III, patients receive imatinib mesylate as in course II.
COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT, or no PBSCT.
COURSE Va (allogeneic PBSCT for patients with HLA-matched sibling donor): Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover.
COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover.
COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation or on day 30 if no transplantation received and continuing for at least 1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain reaction assays at least 3 months apart or until relapse.
After completion of study treatment, patients are followed up monthly for 1 year, every 3 months for 2 years, every 6 months for 2 years, then yearly for up to 10 years.
- Histologically confirmed acute lymphoblastic leukemia (ALL)
- Disease in complete or partial remission after 1 course of induction chemotherapy comprising 1 of the following: intensive 4- or 5-drug regimen on a CALGB or SWOG ALL protocol for previously untreated ALL; any standard induction regimen without enrollment on a cooperative group frontline protocol
- BCR-ABL positive by reverse transcriptase-polymerase chain reaction or fluorescent in situ hybridization OR detection of t(9;22)(q34;q22) or 3-way variant by metaphase cytogenetics
- All patients must also be enrolled on protocol CLB-9862
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study participation
- No other concurrent chemotherapy
- No concurrent steroids except for adrenal failure
- No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
- No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease
- No more than 6 weeks of prior imatinib mesylate during induction therapy
Trial Lead Organizations/Sponsors
National Cancer Institute
|Meir Wetzler||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00039377
ClinicalTrials.gov processed this data on October 17, 2013
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